Cardioprotective Properties of Natural Anti-Platelet Activating Factor Extract From Winery By-products in Healthy Women (NAPE)

Investigation of in Vivo Anti-inflammatory and Anti-platelet Mechanisms of Natural Extract by Modulating PAF Metabolism and Actions

The purpose of this study is to investigate the anti-platelet and anti-inflammatory properties of a winery by-products extract as well as to detect extract compounds and their metabolites in biological fluids. The study is a randomized, double-blind, crossover, placebo controlled postprandial study in healthy women.

Study Overview

• Status: Unknown
• Conditions: Platelet Aggregation and Inflammation
• Intervention / Treatment: Behavioral: Supplement; Behavioral: Placebo

Detailed Description

The well-known cardioprotective and metabolic effects of wine consumption are mainly attributed to its micro-constituents. Grape pomace (GP) is a by-product of the winemaking process and consists mainly of skins and seeds. Winery by-products are a cheap and rich source of similar-to wine micro-constituents, which can be used either to enrich other foods or to be included in food supplements targeting the prevention or partially the therapy of cardiovascular diseases.In this line, our previous results revealed the potent in vitro anti-platelet effects of a specific ethanol-water extract rich in Platelet-Activating Factor inhibitors from winery by-products.

The purpose of this study is to investigate the in vivo anti-platelet and anti-inflammatory properties of the specific winery by-products extract as well as to detect the extract compounds and their metabolites in biological fluids.

Therefore a randomized double-blind, crossover, placebo controlled postprandial study in healthy women will be implemented. For this purpose, 15 healthy women will participate in the protocol. The two daily trials will take place during specific days based on their menstrual cycle. Three days before each blood collection the volunteers will be instructed to abstain from food and beverages rich in phenolic compounds and their dietary intake will be recorded (three 24h recalls and one food frequency questionnaire). The blood collections will be carried out after 8h fasting. At trial day, the volunteers will bring the first morning urine sample and anthropometric measurements will take place (weight, height, waist/hip circumference, bioelectrical impedance). Then a venous catheter will be placed and after 10 minutes the fasting blood will be collected. Volunteers will proceed to the consumption of a standardized meal (1131 kcal, 19.7% carbohydrates, 11.2% protein, 66.7% fat) along with the capsules (study extract or placebo). The type of the capsules consumed (study extract or placebo) will be randomized and blind during the two intervention days for both volunteers and investigators. Blood will be drown after the meal consumption and for the next 6h (every 30minutes for the first 4h and every 1h for the next 2h). Serum, plasma, platelet-rich plasma, leukocyte-rich plasma and urine samples will be isolated at certain time points during trial days so that the anti-platelet, anti-inflammatory and antioxidant effects of the study extract can be evaluated.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 17671
    • Recruiting
    • Department of Nutrition-Dietetics, Harokopio University
    • Contact: Elizabeth Fragopoulou, PhD; Phone Number: 0030 2109549249; Email: efragop@hua.gr
    • Principal Investigator: Elizabeth Fragopoulou, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Healthy
• Females
• BMI: 22-32 kg/m2

Exclusion Criteria:

• Systematic medication
• Chronic disease conditions
• Specific dietary conditions (vegeterian, vegan...)
• Eating disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Supplement; Ethanol-water extract of winery by-products	Behavioral: Supplement; A sufficient quantity of the winery by-products will be extracted on an industrial scale and capsules will be produced, each one containing 110mg of phenolic compounds (gallic acid equivalents).Volunteers will consume 6 capsules along with a standardized meal (1131 kcal, 19.7% carbohydrates, 11.2% protein, 66.7% fat) and blood will be drown before the meal consumption and at specific time points for the next 6h
Placebo Comparator: Placebo; Maltodextrin-based placebo	Behavioral: Placebo; A look-alike placebo containing maltodextrin will be prepared.Volunteers will consume 6 capsules along with a standardized meal (1131 kcal, 19.7% carbohydrates, 11.2% protein, 66.7% fat) and blood will be drown before the meal consumption and at specific time points for the next 6h

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect on platelet aggregation	% Change of EC50 value of platelet aggregation against PAF	Change between timepoints (before meal consumption, 30min, 90min, 150min, 210min, 300min) of the 6hour trial and between the two different interventions
Effect on platelet aggregation	% Change of EC50 value of platelet aggregation against ADP	Change between timepoints (before meal consumption, 30min, 90min, 150min, 210min, 300min) of the 6hour trial and between the two different interventions
Effect on platelet aggregation	% Change of EC50 value of platelet aggregation against Collagen	Change between timepoints (before meal consumption, 30min, 90min, 150min, 210min, 300min) of the 6hour trial and between the two different interventions
Effect on inflammatory markers	Change in PAF biosynthetic enzymes activity (lyso-PAF AT)	Change between timepoints (before meal consumption, 60min, 120min, 180min, 210min, 240min, 300min, 360min) of the 6hour trial and between the two different interventions
Effect on inflammatory markers	Change in PAF biosynthetic enzymes activity (PAF-CPT)	Change between timepoints (before meal consumption, 60min, 120min, 180min, 210min, 240min, 300min, 360min) of the 6hour trial and between the two different interventions
Effect on inflammatory markers	Change in PAF levels Change in PAF degradation enzyme activity (Lp-PLA2) Change in PAF levels IL6	Change between timepoints (before meal consumption, 60min, 120min, 180min, 240min, 360min) of the 6hour trial and between the two different interventions
Effect on inflammatory markers	Change in PAF degradation enzyme activity (Lp-PLA2)	Change between timepoints (before meal consumption, 0min, 30min, 60min, 90min, 120min, 150min, 180min, 210min, 240min, 300min, 360min) of the 6hour trial and between the two different interventions
Effect on inflammatory markers	IL-6	Change between timepoints (before meal consumption, 0min, 30min, 60min, 90min, 120min, 150min, 180min, 210min, 240min, 300min, 360min) of the 6hour trial and between the two different interventions

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect on classical biochemical markers	Total serum cholesterol	Change between timepoints (before meal consumption, 0min, 30min, 60min, 90min, 120min, 150min, 180min, 210min, 240min, 300min, 360min) of the 6hour trial and between the two different interventions
Effect on classical biochemical markers	LDL-cholesterol	Change between timepoints (before meal consumption, 0min, 30min, 60min, 90min, 120min, 150min, 180min, 210min, 240min, 300min, 360min) of the 6hour trial and between the two different interventions
Effect on classical biochemical markers	HDL-cholesterol	Change between timepoints (before meal consumption, 0min, 30min, 60min, 90min, 120min, 150min, 180min, 210min, 240min, 300min, 360min) of the 6hour trial and between the two different interventions
Effect on classical biochemical markers	TAG	Change between timepoints (before meal consumption, 0min, 30min, 60min, 90min, 120min, 150min, 180min, 210min, 240min, 300min, 360min) of the 6hour trial and between the two different interventions
Effect on classical biochemical markers	uric acid	Change between timepoints (before meal consumption, 0min, 30min, 60min, 90min, 120min, 150min, 180min, 210min, 240min, 300min, 360min) of the 6hour trial and between the two different interventions
Effect on classical biochemical markers	Glucose	Change between timepoints (before meal consumption, 0min, 30min, 60min, 90min, 120min, 150min, 180min, 210min, 240min, 300min, 360min) of the 6hour trial and between the two different interventions
Effect on classical biochemical markers	Insulin	Change between timepoints (before meal consumption, 0min, 30min, 60min, 90min, 120min, 150min, 180min, 210min, 240min, 300min, 360min) of the 6hour trial and between the two different interventions
Detection and estimation of extract compounds metabolites		Change between timepoints (before meal consumption, 60min, 120min, 240min, 360min) of the 6hour trial and between the two different interventions

Collaborators and Investigators

• Sponsor: Harokopio University

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2020
• Primary Completion (Anticipated): June 20, 2021
• Study Completion (Anticipated): June 20, 2021

Study Registration Dates

• First Submitted: June 15, 2020
• First Submitted That Met QC Criteria: June 17, 2020
• First Posted (Actual): June 18, 2020

Study Record Updates

• Last Update Posted (Actual): June 18, 2020
• Last Update Submitted That Met QC Criteria: June 17, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: platelet aggregation; anti-inflammatory; healthy women; winery by-products; natural extract; postprandial study; Platelet-activating factor
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: HarokopioU_anti-PAF extract

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No